Spores and Toxins, Questionnaire Example

You are the Chief Scientist (a CSO really) of Rapid Diagnostic Systems, Inc. a newly formed biotechnology company that has just been awarded a handsome bioterrorism grant to design and develop an instrument that specifically detects bacterial spores, not bacteria, spores.

Name the two most important select microorganisms (genus and species) that you would concentrate on.

The two most important select microorganisms that I would concentrate on in awarded a grant to design and develop an instrument that detects bacterial spores is Bacillus anthracis and Clostridium botulinum.

If you were charged with designing a biosensor for detecting spores, what molecule would you target? Hint: What is absolutely unique about bacterial spores that you could take advantage of?

The molecule that would be targeted in in charge of designing a biosensor for detecting spores would be peptidoglycan. This protein is found on the spore coat. Targeting peptidoglycan on the coat can help expel the spore contents and destroy the spore. The membrane coat is responsible for surrounding the spore and creating the double membrane layer that allows for the coat to be tough and durable. Breaking the outer wall will then help destroy the center of the endospore in which the DNA is located. (Cornell University, 2013)

Bacillus anthracis is a Category A biothreat agent. The virulence of this organism is closely linked to several mechanisms but the two most important include its capsular protein (poly-D-glutamic acid) which prevents the host’s neutrophils from phagocytizing the bacteria and a tripartite protein toxin known as anthrax toxin.)

There are three factors that influence the mechanism of action for the toxin in anthrax. In fact, toxins can still remain in circulation after antibiotic treatment causing death. There are three genes that produce the antrax toxin, lethal factor (LF), protective antigen (PA) and edema factor (EF). The toxins enter the cells through the recognition of cellular receptors in the plasma member of the protective antigen. The protective antigen undergoes proteolytic cleavage and then changes into pore-like structures in the plasma membrane. The other two factors, LF and EF then bind to the protective antigen pore and then enter the antigen through receptor mediated endocytosis. The acidic pH causes a change, which the PA then releases, the LF and EF into the cytoplasm where the LF cleaves MAP kinases (MAPKK1 and MAPKK2). This inhibits pathways causing cell death. (Croston)

In the context of this course’s title and the assignment’s focus , carefully read and consider the following hypothetical patient case history (30 points)

Day 1: lives in Los Angeles, CA, feels fine
Day 2: headache, dry mouth, nausea, afebrile, buys Tylenol
Day 3: mucus in throat, difficulty swallowing solid food, dizziness, calls LA nurse hotline
Day 4: difficulty moving eyes, blurred vision, indistinct speech, sees private doc
Day 5: worsens, extreme weakness, calls ambulance, goes to the ER
Day 6: admitted to UCLA hospital, upper and lower paralysis
Day 7: critically ill, ICU
Day 8: dies, respiratory failure
Day 9: notification of sustained increase of patients presenting with these symptoms in LA; and, absence (no connection) of any common dietary exposure among temporally clustered patients has been confirmed. Consider the above case and answer each question, a through e:
a. What surveillance system would be most applicable here? Traditional, Syndromic, PulseNet, or ESSENCE I? PICK ONLY ONE OF THESE ANSWERS

The Essence surveillance system would be most applicable because electronic data is entered into a system and information is used based on the number of visits greater than expected for facilities based on historical data.

Which would be most indicative or most concerning of a biological attack: diffuse increase of such patients across the city or geographic clustering?

Geographic clustering would be most indicative or most concerning of a biological attack because it is an indication of an outbreak in a specific area.

What data source would be most important to accommodate Traditional Surveillance?

The Electronic surveillance system using electronic records would be the most important source to accommodate Traditional Surveillance.

Syndromic surveillance is best run by whom?

Hospitals and health care professionals would run the syndromic surveillance because the data can be entered into electronic health records. The health records can then be monitored by public health agencies.

What’s going on here? What did this person die from and why did this person
die?

The patient acquired inhaled anthrax. He exhibited the symptoms, such as fever, respiratory problems, confusion etc, and the symptoms worsened with progressing time. The patient died because he did not receive treatment in time. He did go to the hospital; however, it was either too late, or the toxins remained in his system after antibiotics were administered.

Bonus -Would a DNA chip device been usable, indeed invaluable in this case for “sniffing out” the cause based on your above scenario? If so, explain.

Yes, a DNA chip could be used. A sample could have been applied to the chip in order to test the chip for anthrax DNA. The DNA elements in the chip would have been able to quickly identify the pathogenic agent. This would decrease time for laboratory results, possibly helping additional cases of anthrax.

With respect to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and their Destruction (4 * 5 pts = 20 points):

What are two major differences between the 1925 Geneva Protocol and the above Convention with respect to biological weapons?

There are differences between the 1925 Geneva Protocol and the Convention on Prohibition of the Development, Production and Stockpiling of Bacteriological and Toxin Weapons and their Destruction. For one, the Geneva Protocol did not indicate the inability to stockpile the weapons; whereas, the convention is taking steps towards an agreement to take measures to exclude any possibility of bacteriological agents and toxins to be used as weapons. In addition, the Geneva Protocol prohibited the use of biological weapons; however, did not prohibit the development of the weapons. (UNOG)

Currently how many countries are non-participants, how many are signatories, and how many have ratified the Convention?

Currently there are 170 State Parties and 13 Signatory States. There are 19 non-signatories states, including Israel that have not signed or ratified the Convention. (NTI, 2013)

What is the difference between a signatory country and one that has ratified the Convention?

Signatory country is one that has signed the agreement and one that ratified the agreement has agreed to follow protocol, but has not signed the agreement.

Why is biodefense research involving Category A, B and C agents not in conflict with the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and their Destruction?

This is not in conflict with the Convention because any purpose used for protective defenses, those purposes related to the protection against toxic chemicals and chemical weapons is allowed under Article II of the Convention. (ICRC, 2013)

PBS Economic correspondent, Paul Solman, declared in his PBS video presentation of Bioterror: The Downside of Innovation “You don’t want your kids to be the first one on the block to make Ebola virus” with respect to the potential use of synthetic biology for “kitchen sink” biological warfare. Describe in one brief paragraph what synthetic biology is as well as how and/or why it can be considered dual-use.

Synthetic biology is a sector of biology in which engineers cellular regulatory systems and the genomes of organisms. The purpose is to develop microchips. This field has made advances in DNA synthesis, which has further enabled the creation of DNA molecules, genes and proteins. An example of synthetic biology is the development of proteins or genes that reprogram living cells to produce cheaper drugs or assist in cancer therapy. In addition, some engineering is aimed towards molecular structure or assembly, which assembles into small structures at the nanometer scale and is used to target diseased cells. The dual use to synthetic biology is the possibility of its misuse, as well as the undermining of life machines versus manufactured machines. Therefore, there are some ethical concerns. (Douglasand Savulescu, 2002)

References

Cornell University. (2013). Bacterial Endospores. Cornell University Department of Microbiology. Retrieved from: http://micro.cornell.edu/research/epulopiscium/bacterial-endospores

Croston. Anthrax Toxin Mechanism of Action. Biocarta. Retrieved from: http://www.biocarta.com/pathfiles/h_anthraxPathway.asp

Douglas, T. and Savulescu, J. (2002). Synthetic Biology and the Dual-Use Dilemma. Oxford Center for Practical Ethics. Retrieved from: http://www.bep.ox.ac.uk/__data/assets/pdf_file/0011/13889/SyntheticBiologyDualUse_v2.pdf

ICRC. (2013). Convention on the prohibition of the development, production, stockpiling and use of chemical weapons and on their destruction. Paris 1993. Retrieved from: http://www.icrc.org/ihl.nsf/52d68d14de6160e0c12563da005fdb1b/3f233cb0f0c580f8c125641f002d42a8?OpenDocument

UNOG. Disarment. Retrieved from: http://www.unog.ch/80256EE600585943/(httpPages)/04FBBDD6315AC720C1257180004B1B2F?OpenDocument

NTI. (2013). Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons (BTWC). Retrieved from: http://www.nti.org/treaties-and-regimes/convention-prohibition-development-production-and-stockpiling-bacteriological-biological-and-toxin-weapons-btwc/